Background: In adulthood, depression is the most common type of mental illness and will be the second leading cause of disease by 2020. Major depression dramatically affects the function of the central nervous system and degrades the quality of life, especially in old age.Several mechanisms underlie the pathophysiology of depressive illness, since it has a multifactorial etiology. Human and an-imal studies have demonstrated that depression is mainly associated with imbalances in neurotransmitters and neurotrophins, hypothalamic-pituitary-adrenal axis alterations, brain volume changes, neurogenesis dysfunction, and dysregulation of in-flammatory pathways. Also the gut microbiota may influence mental health outcomes.Although depression is not a consequence of normal aging, depressive disorders are common in later life, even if often undi-agnosed or mis-diagnosed in old age. When untreated, depression reduces life expectancy, worsens medical illnesses, en-hances health care costs and is the primary cause of suicide among older people. To date, the underpinnings of depression in the elderly are still to be understood, and the pharmacological treatment is the most commonly used therapy.Objective:Since a sedentary lifestyle and poor eating habits have recently emerged as crucial contributors to the genesis and course of depression, in the present review, we have focused on the effects of physical activity and omega-3 fatty acids on depressive illness in the elderly.Results: A growing literature indicates that both exercise and dietary interventions can promote mental health throughout one’s lifespan.Conclusion: There thus emerges the awareness that an active lifestyle and a balanced diet may constitute valid low-cost pre-vention strategies to counteract depressive illness in the elderly.